Download Drug Interactions with Tobacco Smoke

Drug Interactions with Tobacco Smoke
Many interactions between tobacco smoke and medications have been identified. Note that in most cases it
is the tobacco smoke—not the nicotine—that causes these drug interactions. Tobacco smoke interacts with
medications through pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms. PK interactions affect the
absorption, distribution, metabolism, or elimination of other drugs, potentially causing an altered pharmacologic
response. The majority of PK interactions with smoking are the result of induction of hepatic cytochrome P450
enzymes (primarily CYP1A2). PD interactions alter the expected response or actions of other drugs. The amount
of tobacco smoking needed to have an effect has not been established, and the assumption is that any smoker
is susceptible to the same degree of interaction. The most clinically significant interactions are depicted in
the shaded rows.
Drug/Class
Mechanism of Interaction and Effects
Pharmacokinetic Interactions
Alprazolam (Xanax®)
• Conflicting data on significance, but possible  plasma concentrations
(up to 50%);  half-life (35%).
Bendamustine (Treanda®)
• Metabolized by CYP1A2. Manufacturer recommends using with caution in
smokers due to likely  bendamustine concentrations, with  concentrations
of its two active metabolites.
Caffeine
• Metabolism (induction of CYP1A2);  clearance (56%). Caffeine levels likely 
after cessation.
Chlorpromazine
(Thorazine®)
•  Area under the curve (AUC) (36%) and serum concentrations (24%).
•  Sedation and hypotension possible in smokers; smokers may require
 dosages.
Clopidogrel (Plavix®)
•  Metabolism (induction of CYP1A2) of clopidogrel to its active metabolite.
• Clopidogrel’s effects are enhanced in smokers (≥10 cigarettes/day):
significant  platelet inhibition,  platelet aggregation; while improved
clinical outcomes have been shown, may also  risk of bleeding.
Clozapine (Clozaril®)
•  Metabolism (induction of CYP1A2);  plasma concentrations (18%).
•  Levels upon cessation may occur; closely monitor drug levels and reduce
dose as required to avoid toxicity.
Erlotinib (Tarceva®)
•  Clearance (24%);  trough serum concentrations (2-fold).
Flecainide (Tambocor )
•  Clearance (61%);  trough serum concentrations (25%). Smokers may
need  dosages.
Fluvoxamine (Luvox®)
•  Metabolism (induction of CYP1A2);  clearance (24%);  AUC (31%);
 plasma concentrations (32%).
• Dosage modifications not routinely recommended but smokers may need
 dosages.
Haloperidol (Haldol®)
•  Clearance (44%);  serum concentrations (70%).
Heparin
• Mechanism unknown but  clearance and  half-life are observed.
Smoking has prothrombotic effects.
• Smokers may need  dosages due to PK and PD interactions.
Insulin, subcutaneous
• Possible  insulin absorption secondary to peripheral vasoconstriction;
smoking may cause release of endogenous substances that cause insulin
resistance.
• PK & PD interactions likely not clinically significant; smokers may need
 dosages.
Irinotecan (Camptosar®)
•  Clearance (18%);  serum concentrations of active metabolite, SN-38
(~40%; via induction of glucuronidation);  systemic exposure resulting in
lower hematologic toxicity and may reduce efficacy.
• Smokers may need  dosages.
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(continued)
Drug/Class
Mechanism of Interaction and Effects
Methadone
• Possible  metabolism (induction of CYP1A2, a minor pathway for methadone).
• Carefully monitor response upon cessation.
Mexiletine (Mexitil®)
•  Clearance (25%; via oxidation and glucuronidation);  half-life (36%).
Olanzapine (Zyprexa )
•  Metabolism (induction of CYP1A2);  clearance (98%);  serum concentrations (12%).
• Dosage modifications not routinely recommended but smokers may need
 dosages.
Propranolol (Inderal)
•  Clearance (77%; via side-chain oxidation and glucuronidation).
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Riociguat (Adempas )
• Plasma concentrations (by 50–60%).
• Smokers may require dosages higher than 2.5 mg three times a day; consider
dose reduction upon cessation.
Ropinirole (Requip®)
•  Cmax (30%) and AUC (38%) in study with patients with restless legs syndrome.
• Smokers may need  dosages.
Tacrine (Cognex®)
•  Metabolism (induction of CYP1A2);  half-life (50%); serum concentrations
3-fold lower.
• Smokers may need  dosages.
Tasimelteon (Hetlioz®)
•  Metabolism (induction of CYP1A2); drug exposure  by 40%.
• Smokers may need  dosages.
Theophylline
(Theo Dur®, etc.)
•  Metabolism (induction of CYP1A2);  clearance (58–100%);  half-life
(63%).
• Levels should be monitored if smoking is initiated, discontinued, or changed.
Maintenance doses are considerably higher in smokers.
•  Clearance with second-hand smoke exposure.
Tricyclic antidepressants
(e.g., imipramine,
nortriptyline)
• Possible interaction with tricyclic antidepressants in the direction of  blood
levels, but the clinical significance is not established.
Tizanidine (Zanaflex®)
•  AUC (30-40%) and  half-life (10%) observed in male smokers.
Warfarin
•  Metabolism (induction of CYP1A2) of R-enantiomer; however, S-enantiomer
is more potent and effect on INR is inconclusive. Consider monitoring INR
upon smoking cessation.
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Pharmacodynamic Interactions
Benzodiazepines
(diazepam,
chlordiazepoxide)
•  Sedation and drowsiness, possibly caused by nicotine stimulation of central
nervous system.
Beta-blockers
• Less effective antihypertensive and heart rate control effects; possibly caused
by nicotine-mediated sympathetic activation.
• Smokers may need  dosages.
Corticosteroids, inhaled
• Smokers with asthma may have less of a response to inhaled corticosteroids.
Hormonal contraceptives
•  Risk of cardiovascular adverse effects (e.g., stroke, myocardial infarction,
thromboembolism) in women who smoke and use oral contraceptives. Ortho
Evra patch users shown to have 2-fold  risk of venous thromboembolism
compared to oral contraceptive users, likely due to  estrogen exposure (60%
higher levels).
•  Risk with age and with heavy smoking (≥15 cigarettes per day) and is quite
marked in women ≥35 years old.
Serotonin 5-HT1 receptor
agonists (triptans)
• This class of drugs may cause coronary vasospasm; caution for use in smokers due to possible unrecognized CAD.
Adapted and updated, from Zevin S, Benowitz NL. Drug interactions with tobacco smoking. Clin Pharmacokinet 1999;36:425–438.
Revised 3/6/15
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